Autism spectrum disorders (ASDs) affect multiple functional systems, including reciprocal social behavior, communication and behavioral regulation. This suggests that multiple brain systems are involved in their pathobiology. This project will use high resolution structural MRI and diffusion tensor imaging (DTI) on participants recruited through the Family Genetics study (Project 2) in order to test several current hypotheses about neural systems affected by ASDs. Our preliminary studies show significant brain volume increases, as well as some regionally specific increases and decreases in ASDs. The literature in these areas is not always consistent, and it seems likely that heterogeneity due to ASD subtypes contributes to uncertainty in this area. By adding to our already large, well characterized sample, we will be in good position to stratify subjects along more informative dimensions, which may involve use of Family Genetics data. We rely heavily on results from our ongoing fMRl studies to guide our selection of brain regions for morphometric analyses. DTI will be used to test the integrity of cerebral white matter. Recent studies have suggested that white matter abnormalities may figure prominently in the pathobiology of the ASDs. We propose to collect MRI data on 120 persons with an ASD, and 50 controls, yielding a combined total of 95 persons with high functioning autism (HFA), 95 persons with Asperger syndrome (AS) and 30 persons with PDD NOS to test the following hypotheses: - Brain volume is increased in persons with an ASD - Cerebral white matter volume is increased in persons with an ASD - Fractional anisotropy is reduced throughout the cerebral white matter, and at boundaries to key gray matter nodes in our model of the social brain - Cross sectional area and fractional anisotropy of the genu and splenium of the corpus callosum is reduced in persons with an ASD, and - The gray matter volume of specific areas of the medial prefrontal cortex, fusiform gyrus, superior temporal sulcus and the amygdala are significantly altered in persons with an ASD.